Month: October 2013

On a recent trip to Indonesia I came across a temple, in a small village outside of Ubhud, where a group of local Balinese were rolling around on yoga mats in fits of hysterical laughter. The sound emanating from the temple walls was quite amazing and, intrigued, we went closer to see what they were doing. What we had stumbled across was a laughing yoga class run by a group called ‘Bali Happy’ who move around Bali promoting laughter as an exercise, with the aim of ridding the local people of their ailments. The lovely group leader invited us in, and explained the principles of the class; apparently there are different ‘sounding’ laughs to treat problems in different areas of the body, such as your gut, lungs, throat, head etc. He explained that the Balinese people were suffering from illness resulting from an unusual spate of weather which had left Bali wetter and colder than usual; and that they were helping people by focusing on the healing properties of laughter. He then invited us to join the class. This amazing experience left me questioning; aside from the psychological, emotional and communicative benefits, what are the biological principles underlying the healing properties of laughter, and could it really be of therapeutic value?

Norman Cousins

The Western ideology for laughter as a medicine began in 1976, when Norman Cousin published his paper ‘Anatomy of an Illness’ which sparked a cascade of enthusiasm for health benefits of this innate, involuntary reaction. But is laughter really the best medicine? Well one thing’s for sure, it can’t hurt. Indeed, unlike many forms of prescribed medication, laughter certainly has no undesirable side-effects. Also a number of studies have highlighted its health benefits.

The act of laughing causes a series of physiological changes. These act rapidly and are often accompanied by many beneficial consequences; particularly to the muscular, respiratory and cardiovascular systems of the body. One of the most frequently reported benefits of laughter is that it exercises and subsequently relaxes many important muscles. In 1979, Cousins described laughing as “a form of jogging for the innards”; this is because when we laugh our whole body becomes involved, leading to the coordinated action of our facial, chest, abdominal, skeletal and even gastrointestinal muscles. Furthermore, after laughing we experience a period of muscle relaxation with assists in reducing tension in the neck, shoulders and abdominals.

Our cardiovascular and respiratory systems stand to benefit too. Laughter causes a prompt increase in heart rate and blood pressure, which can improve circulation. This, coupled with an elevated respiratory rate, respiratory depth and oxygen consumption, improves the rate of residual air exchange and ventilation. These physiological changes are followed by a drop in heart rate, respiratory rate and blood pressure. Indeed, research has identified an inverse association between the propensity to laugh and coronary heart disease. Laughter has also been suggested as an adjuvant therapy to reduce the risk of heart attack in high-risk diabetic patients. For a review of the health benefits of laughter, see here.

Studies have also identified that the muscle exertions involved in producing laughter may have a stimulatory effect on the production of endorphins. Endorphins are opioid compounds that stimulate feelings of euphoria and lower pain thresholds. It is widely accepted that a patient’s emotional state will often affect the course of a disease. Therefore any therapy which encourages positive emotions in patients may ultimately improve their prognosis.

Interestingly, laughter therapy it is one of the most frequently used complementary therapies in cancer patients worldwide. It’s success most likely stems from the observation that laughter can reduce stress levels. Any therapy which successfully reduces stress certainly can’t be a bad thing; especially since studies have correlated both laughter and reduced stress with improvements in immune function and increases in pain tolerance. Some studies even suggest that laughter may increase disease resistance. The precise mechanism of this is yet to be defined, but may be linked to attenuation of serum levels of the ‘stress hormone’ glucocorticoid. Glucocorticoids are known to suppress the immune system, making stressed individuals more susceptible to disease. So, in it’s action on the neuroimmune system, it seems that laughter can directly improve disease resistance, by manipulating our innate immune responses and reducing glucocorticoid levels.

Given the known psychological benefits of a positive emotional state, it’s not surprising that laughter therapy has also been suggested to have clinical applications for neurological diseases like dementia and schizophrenia. As with most serious illnesses, dementia can place both sufferers and their families under high levels of stress. Since stress is believed to negatively affect an individuals cognitive ability, this may exacerbate symptoms. Laughter therapy has been suggested as a way of reducing stress in both patients and their families. Indeed, when a positive attitude is shared by patients, families and staff, it can have a positive effect on the emotional-affective and cognitive functioning of the patients.

Laughter has helped patients to withdraw from feelings of irritability, stress, tension, and counteract symptoms of depression; it elevates self-esteem, hope and energy, promotes memory, creative thinking and problem solving; increases aspects of self-efficacy and optimism and improves relationships and general quality of life. In other neurological diseases like schizophrenia, laughter has been shown to reduce hostility, depression and anxiety scores and encourage social competence.

Although complementary therapies such as this are not meant to replace mainstream treatment and are not promoted to cure disease. They may often be effective in controlling symptoms, improving well-being and quality of life. While laughter research is still in it’s infancy, there is much to be said for its numerous psychological and physiological benefits and the potential for it to become a very successful complementary and alternative therapy. With laughter as an exercise emerging into the main-stream, through clubs like laughing yoga, it appears that laughter-based interventions are gaining more acceptance, and hopefully further scientific study will follow as a result. As laughter medicine continues to generate more medical and public interest, it may be important to consider that along with eating your vegetables, exercising regularly and getting enough sleep, laughter is a wonderful way to enhance your health. Most importantly, as demonstrated here, there are more than a few reasons to conclude laughter is, and could in the future be, a widespread and effective complimentary intervention for many diseases.

On October 10th 2013, there were headlines on the front pages of several British papers claiming that “A simple pill may cure Alzheimer’s”. These papers included the Times (£) and the Independent, who both put the stories on their front pages, the BBC website and breakfast show. The story was also tweeted by these outlets as well as America’s Fox News:

This breakthrough in treatment for Alzheimer's could very soon pave the way for a simple pill to cure the disease. http://t.co/hFBUSdr38R

As a scientist who has worked on Alzheimer’s disease, headlines like this always provoke my cynical side. I’ve seen stories proclaiming a cure many times before, yet no cure is forthcoming. My cynicism was somewhat rewarded when I researched the story further. The study did indeed find that a pill, which inhibits a protein called PERK, was able to prevent brain cell death in mice which showed symptoms of disease. However, the disease the mice had was not Alzheimer’s; they had a prion disease.

In order to understand the research, here’s a quick explanation. Prions are misfolded, infectious proteins which are linked to neurodegenerative diseases such as BSE (or “mad cow disease” as it was known in the 80s) and CJD in humans. Alzheimer’s is also caused at least in part by a misfolded protein, called amyloid-beta (Aβ). Both prions and Aβ are affected by something called the Unfolded Protein Response (UPR) in cells. The UPR detects the misfolded protein and stops the brain cell making any new proteins. This means that the cell cannot make proteins which are essential to its survival and so will eventually die, leading to neurodegeneration.

Don’t get me wrong, the results from the study are promising. However, the newspaper headlines are incredibly misleading. There are some key problems with interpreting the research as a “cure for Alzheimer’s”:

This study only theoretically applies to Alzheimer’s disease as the authors note that Aβ is subjected to the same UPR as prions. The effects of the drug will need to be tested on Aβ before any definitive conclusion can be made about its effectiveness in treating Alzheimer’s. Furthermore, Alzheimer’s disease has other contributory destructive mechanisms not related to the UPR which also need to be assessed. The same is true before a link can be made to the other neurodegenerative diseases mentioned in the paper, such as Parkinson’s or ALS.

The research was conducted in mice rather than humans and there is no guarantee that the drug will be usable in humans. It may not have the same effects or the side effects may render the drug unusable.

The drug causes potentially serious side effects in mice such as mild diabetes and weight loss. This would have to be rectified before the drug can be administered to humans which could take a significant amount of time.

The weight loss side effect in mice means that they could not be used for a long time and it is unknown what the long term effects of the drug are. Something which targets both the brain and an essential cellular process such as the UPR may have detrimental effects if used over a long period of time.

The pill does not “cure” memory loss. The mice that were treated with the drug did not regain memories which were already lost. However, treating these mice did prevent the disease from progressing further. This pill will not help people who already suffer from mid to late-stage dementia.

Even if the drug is suitable for use in humans, it will have to go through clinical trials before being put to regular use. This will take years, possibly even decades.

Most of the newspapers covering this story did mention some of these problems. The Independent in particular made it very clear the study was in mice and a cure is “a long way off”. (However, in their tweet (above) they say that, “This breakthrough in treatment for Alzheimer’s could very soon pave the way for a simple pill to cure the disease.” showing the differences in these types of news communication). The Express, on the other hand, took seven lines to even mention that the study was in mice. Unfortunately, in this day and age, many people don’t read further than the headline, sub-heading and possibly the first two or three paragraphs. Many people therefore may well get the impression that a cure for Alzheimer’s is imminent and misunderstand the point of the study.

Later on in the day when things had calmed down a bit many newspapers did write editorials (for example in the Independent and the Guardian). These mostly highlighted some of the points above and clarifying that there is still a long way to go in curing Alzheimer’s. But this is after the damage had been done, the headlines had been seen and the tweets had been sent. The point is that the story should never have been given so much prominence in the first place.

It’s quite easy to assess how people are reacting to a story by use of Twitter. A quick search of “Alzheimer’s” on the day the story broke showed a lot of people re-tweeting the story from various news sources, some with a link, some without. The misleading nature of the headline can be seen by the nature of some of these tweets, including one which said “They’ve found a cure for Alzheimer’s. This is big”. One of the big tweeters was the comedian Jimmy Carr, who tweeted this (rather lame) joke:

Great news, scientists have found a cure for Alzheimer's, I'll never forget this day….if it works.

With no link to the story, how are people supposed to know where he got the information from? Another problem with today’s microblogging news delivery system is that there isn’t a lot of room for details and so the story can easily get mutated.

There were some expressing cynicism. The Alzheimer’s Society stated “This is a promising development as it shows this biological pathway is a potential target for new treatments. However, it is important to note that this study was carried out on mice with prion disease and so it is not clear how applicable it is to humans with diseases such as Alzheimer’s.”

But it’s not the users of Twitter who I am concerned about. The problem with misleading story reporting like this is the effect it has on sufferers of the disease or their relatives. The reason this particular story has got me angry is because I have seen the effects that this sort of reporting can have. Long-term readers will be aware that my grandmother suffered from Alzheimer’s Disease, which took a huge toll on my grandfather.

I still clearly remember a day when a national tabloid newspaper carried the headline “Vaccine for Alzheimer’s Disease!” My grandfather read the headline, turned to me and said “Does this mean they’ll be able to cure your grandmother?” My cynicism piqued, I read the article and had to gently tell him no. That story held many of the same points as this one; it was a study done in mice and no human trials had been conducted. It is five years later and there is no news on that subject; whether it failed at clinical trials or is still being tested I don’t know. But the false hope it gave to my grandfather, and the countless others who read these headlines and think their disease may be cured soon, is a sad and dangerous thing.

Who is to blame for this misinformation spreading? It’s probably a subtle combination of the scientists who wrote the paper, the journal who published it and the reporters who wrote the newspaper stories. For scientists, having work published in national newspapers is a huge coup; national reports result in interest in your work and so you’re more likely to secure funding to continue with your groundbreaking research. Unfortunately, newspapers and by extension their readers will mostly respond to “interesting” stories, which translates to “treating a disease that people have heard of”.

Alzheimer’s is big news now, as it is predicted to affect 1 million people by 2021. Therefore, the scientists probably put Alzheimer’s as the key point of the findings to increase interest in their research. This is a common practise amongst researchers desperate to secure funding from a dwindling pot. I noted when researching this post that every single headline said the more evocative “Alzheimer’s” rather than “Parkinson’s Disease” or “ALS” which were also mentioned in the research paper as potential beneficiaries of the drug. Curiously, CJD isn’t even mentioned by the researchers as a disease which can benefit from the treatment despite being the best-studied prion disease in humans. However, CJD is much rarer than Alzheimer’s (causing 1 death per 1-2 million of the population) and the media storm that happened around it in the 90’s has died down. It is not a “sexy” enough disease to sell research or newspapers on such a grand scale.

How is this problem going to be solved? Is it possible to make research interesting if it’s not linked to a disease? I would like to think it would, but them I’m biased. It’s a real bugbear for me as a biologist that an “interesting” story about biological research has to be about curing a disease. Research which just explains how a system works can be fascinating.

Certainly taking out a small, speculative point and blowing it up to the key part of the story doesn’t work. However an accurate headline such as “There’s a drug which prevents brain cell death in mice that have something similar to Alzheimer’s disease; won’t be used in humans for a decade or so” is hardly catchy. But it should be made crystal clear in the very first reading points of the article exactly what has been found and its relationship to the disease; the authors and journalists at least owe that to the people affected. As a reader, it’s probably best to take headlines involving the words “cure” and a deadly disease with a pinch of salt until you’ve read the full article. Unless they involve the words “repeated successful human trials” then it’s probably best to treat the information with caution.

“Ten years ago, James Watson testified to Congress that once we had the genome sequenced, we would have the language of life. But it turns out that it’s a language we don’t understand.” Robert Best, 2013

In April 2003, at a cost of $2.7bn, the human genome was announced to great pomp and ceremony. This would reveal the deepest secrets of biology, give us the blueprint to create a human and disclose how diseases develop. But 10 years on, has the Human Genome Project been a true medical breakthrough and what role does it play in medical treatment today?

The Human Genome Project was headline busting. This was an international collaboration like no other, which would be the shining peak of human endeavour. Being able to look into an individual’s DNA would give us new knowledge about what caused diseases. What’s more, this would herald a new era in medicine whereby we could use this to diagnose diseases years before a patient felt any symptoms and tailor their treatment to their own personal needs.

Unfortunately, passionate headline-filling coverage has waned recently. The human genome is sadly a lot more complex than we had hoped. The quote above, from geneticist Bob Best, sums up the current state of genome sequencing. Speaking to the Guardian’s Carole Cadwalladr in her excellent first-hand account of how it feels to get your own genome sequenced, Dr. Best hits the nail on the head. We can now sequence a whole human genome for $5,000. That part of the technology has accelerated forward. What remains however, is the pining question of what it all means.

The first problem is that the most common diseases seem more complicated than we had hoped. Instead of being one disease caused by one gene, these diseases seem to be lots of smaller diseases caused by many different genes, conspiring to produce similar results. This is the most evident in cancer. People like to group cancers together into one disease but in reality, there are many, varied faulty processes that can cause a cancer to develop.

One can now do an experiment whereby you measure the genomes of a group of cancer patients and compare them to the genomes of a group of healthy volunteers. Unfortunately, this gives you many, subtle deviations and not one Holy Grail ‘cancer gene’.

Genome sequencing has given rise to the potential for personalised treatments. We know that the best treatments we currently have do not work for all patients. This fits with the knowledge that these diseases are actually different diseases all showing similar symptoms. By understanding which small subset of disease a patient is showing and how a patient might deal with a drug, we can tailor the treatment accordingly. The way this technology can be used is explained excellently in this animation. At this stage, we have increasing numbers of great success stories from rare genetic diseases, but limited success in the most common diseases.

This could be because the genome only tells us what may be happening in a living organism. Genes contain the instructions to make life; on their own they do nothing. It is the proteins that are made from these instructions that are the true machines of the living world. Proteins are made from genes via processes known as transcription and translation (see picture below). How a protein is made from the instructions in a gene can be impacted by many lifestyle and environmental factors. This is exactly why lifestyle and environmental factors play such a huge part in disease.

One’s genes do not tell us everything, they only contain the instructions. It is the proteins they make that are the true workhorses of the living world. Genes contain the instructions to make proteins via processes known as transcription and translation. These are impacted by environment, lifestyle and disease.

There are leaps and bounds being made in the field of proteomics. This is the process in which proteins, as opposed to genes, are measured. By measuring the proteome (all the proteins in a cell) we can now see what the genes are doing. We can see which genes are more active than others by seeing how much of the respective protein is being made. The vast complexity of this comes when people can have very similar genes, but widely different combinations of proteins they make from them. The human genome contains roughly 21,000 protein-encoding genes. These are responsible for the production of an estimated 250,000 – 1 million proteins. Measuring someone’s genome alone will not tell you exactly what is going on within their bodies.

Albeit technically difficult, analysing the proteome of patients has the potential to tell you which subset of disease patients may have, it can tell you which faulty genes are the most harmful, and can give you possibilities for new treatments. We hope that what goes on beyond a person’s genes will unlock further understanding of disease and truly bring in the era of personalised medicine.

The Human Genome Project has and will continue to open up new realms of possibility for understanding more about life. It has given us the basis to build on our knowledge of how we are made and the beginning to personalised medicine. However, there is still a very long way to go. It is the proteins inside you that truly define health and disease. Until we understand more about how specific genes make specific proteins and how this is impacted in common diseases, we will only be scratching the surface of the potential personalised medicine has to revolutionise treatment.